Evidence of prokineticin dysregulation in fallopian tube from women with ectopic pregnancy

Objective: To demonstrate expression and regulation of prokineticins (PROKs) and their receptors (PROKRs) in fallopian tube (FT) from women who are not pregnant and women with ectopic pregnancy (EP). Design: Tissue analysis. Setting: Large United Kingdom teaching hospital. Patient(s): Women undergoing hysterectomy for benign gynecological conditions (n = 15) and surgery for EP (n 16). Intervention(s): Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine FT PROK/PROKR messenger RNA (mRNA) expression and protein localization, respectively. The PROK/PROKR levels were measured in tubal explant cultures stimulated with estrogen (E) and progestogen. Main Outcome Measure(s): Differential expression of PROK and PROKR. Result(s): The FT PROK2 and PROKR1 mRNA levels were up-regulated during the P-dominant midluteal phase of the menstrual cycle. Increased PROKR1 expression was observed in tubal explant cultures treated with medroxyprogesterone acetate (MPA). The PROK and PROKR proteins were localized to the epithelium and smooth muscle layers of the FT. The PROKR1 and PROKR2 mRNA levels were lower in FT from women with EP compared with nonpregnant FT from the midluteal phase. Conclusion(s): These data suggest a potential role for PROKs in FT function. The PROKs are known to affect smooth muscle contraction in the gut. Dysregulated PROK expression in FT could affect FT smooth muscle contractility and embryo-tubal transport, providing a potential cause for EP. (Fertil Steril (R) 2010;94:1601-8. (C) 2010 by American Society for Reproductive Medicine.)